IL-18 induces a marked gene expression profile change and increased Ccl1 (I-309) production in mouse mucosal mast cell homologs.
Helminthic infections, which are particularly common in the developing world, are associated with the accumulation of mucosal mast cells (MMCs) in the epithelial layer of the gut. Although intestinal parasite infection models argue that IL-18 plays a role in MMC differentiation and function, the direct effect of IL-18 on MMCs is still not well understood. To clarify the role of IL-18 in mast cell biology, we analyzed gene expression changes in MMCs in vitro. DNA microarray technology uncovered a group of chemokines regulated by IL-18, among which Ccl1 (I-309, TCA-3) showed the highest up-regulation. Ccl1 induction was only transient in mast cells and was characteristic for both immature and mature MMCs, but not for connective tissue-type mast cells. IL-18 exerts its Ccl1-inducing effect in MMCs primarily via the activation of NFkappaB. Moreover, IL-18 was effective both in the absence and the presence of IgE-antigen complex. The Ccl1 receptor (CCR8) is known to be expressed by T(h)2 cells and is involved in their recruitment. Our present findings suggest that IL-18 may contribute to mast cell-influenced Th2 responses by inducing Ccl1 production.
Wiener
Zoltan
Z
Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Nagyvarad ter 4, Hungary.
Pocza
Peter
P
Racz
Melinda
M
Nagy
Gyorgy
G
Tolgyesi
Gergely
G
Molnar
Viktor
V
Jaeger
Judit
J
Buzas
Edit
E
Gorbe
Eva
E
Papp
Zoltan
Z
Rigo
Janos
J
Falus
Andras
A
D000818:Animals; D054402:Chemokine CCL1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004140:Dinitrophenols / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018928:Immunity, Mucosal; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
C502258:Ccl1 protein, mouse; D054402:Chemokine CCL1; D004140:Dinitrophenols; D020382:Interleukin-18; D016328:NF-kappa B; D012709:Serum Albumin; C058064:dinitrophenyl-human serum albumin conjugate; D009569:Nitric Oxide